What is Translational Research?

Transcription

1 University of Massachusetts Medical School UMass Center for Clinical and Translational Science Research Retreat 2011 UMass Center for Clinical and Translational Science Research Retreat May 20th, 8:30 AM - 9:00 AM What is Translational Research? Catarina I. Kiefe University of Massachusetts Medical School Follow this and additional works at: Part of the Community-Based Research Commons, Educational Assessment, Evaluation, and Research Commons, Health Services Research Commons, Science and Technology Studies Commons, and the Translational Medical Research Commons This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License. Kiefe, Catarina I., "What is Translational Research?" (2011). UMass Center for Clinical and Translational Science Research Retreat This material is brought to you by escholarship@umms. It has been accepted for inclusion in UMass Center for Clinical and Translational Science Research Retreat by an authorized administrator of escholarship@umms. For more information, please contact Lisa.Palmer@umassmed.edu.

2 What is Translational Research? Catarina Kiefe, MD, PhD University of Massachusetts Medical School Dept of Quantitative Health Sciences May 20, 2011

3 DISCLOSURE I have no actual or potential conflict of interest in relation to this program or presentation. 2/24

4 Overview Translational Science Why? What? The translational spectrum: a changing nomenclature Bench to beside : a limited paradigm Wrong endpoint (bedside) Wrong direction: what about bedside to bench? Charge for the day 3/24

5 Why Translational Science? Median time from description of a new discovery in a basic science journal to publication of use of this discovery in a highly cited article in the medical literature: 24 years Contopoulus-Ioannidis, Science, Sept 2008 Mean time to implement a new clinical research finding into practice: 17 years Balas, Boren, Yearbook Medical Informatics, /24

6 Translational Blocks in the Clinical Research Continuum Copyright restrictions may apply. Sung, N. S. et al. JAMA 2003;289:

7 Translational Research in US Introduced as part of NIH Roadmap Zerhouni. The NIH Roadmap. Science 2003 (302:63-72) NIH Definitions used in CTSA funding (e.g. RFA-RM ) Clinical research comprises studies and trials in human subjects Translational research includes two areas of translation: Applying findings from laboratory research and preclinical studies to the development of trials and studies in humans Enhancing the adoption of best practices in the community 6/24

8 Translational Research in Europe UK Cooksey Report: Process of taking the findings of either basic or clinical research to produce innovations in health care settings Cooksey The Stationery Office. London The European Advanced Translational Research Infrastructure in Medicine (EATRIS) Becker and vandongen. J Cardiovasc Trans Res 2011 Funded in part by European Union, to be established through both public and private funds Maintain Europe's competitiveness in biomedical research and health industry 7/24

9 Adapted from Waldman and Terzic. Clin Transl Sc (5):

10 Adapted from Waldman and Terzic. Clin Transl Sc (5):

11 Adapted from Waldman and Terzic. Clin Transl Sc (5):

12 The Broad Spectrum of Biomedical Research: Genomics Khoury et al. Genet Med 2007:9(10): T0: Genome T1: Moves genome-based discovery into candidate health application (eg genetic tests) T2: Assesses value of application for health practice, leads to evidence-based guidelines T3: Moves guidelines/evidence into practice T4: Evaluates real world health outcomes of genomic applications T5: Studies genomics in the context of the social determinants of health <3% of genomic research focuses on T2 T5 11/24

13 T1 vs. T2+: Changing Boundaries Initially, translational research required whole humans or human population groups as study units. Evolving nomenclature: T1 research takes knowledge from the bench ( wet lab ) to clinical knowledge Initially: Phase1-3 clinical trial (including RCTs) Recently: also T0, mice, even cells T2+ research takes clinical knowledge into realized human benefit E.g. Group-randomized implementation trials Recently: also phase 3 clinical trials 12/24

14 T1 versus T2+ Research T2+ defining elements: dry lab research that uses statistics and epidemiology as its basic tools The study units may be individual humans, groups of humans (populations), or health systems T1 defining elements: May also use wet lab tools but used to involve whole humans Study unit now from lab animal to individual patient Cultural innovations for both: Transdisciplinary, team science Bidirectionality as emerging concept 13/24

15 Overview Translational Science Why? What? The translational spectrum: a changing nomenclature Bench to beside : a limited paradigm Wrong endpoint (bedside) Wrong direction: what about bedside to bench? Charge for the day 14/24

16 Example : Type 2 Diabetes Prevention Chronic hyperglycemia causes severe endorgan damage through fairly well understood pathopysiology (T0, T1) T0-T1 research has resulted in multiple medications that control hyperglycemia Solid clinical research links Type 2 diabetes to overweight/obesity (T2 - T3): the diabesity epidemic 15/24

17 The diabesity epidemic Why T2+ Research? Prevalence of obesity among men in the US With a parallel rise in the incidence of diabetes Freedman MMWR

18 Important Translational Question Weight loss and other lifestyle modifications improve glucose control in patients with diabetes Can lifestyle modification and weight reduction PREVENT diabetes? 17/24 17

19 Diabetes Prevention Program (DPP) RCT : 3,234 persons at 27 centers, followed for 10 years Knowler, NEJM 2002; Knowler, Lancet 2009 Cumulative incidence of DM2 lowest in lifestyle group: 58% lower incidence at 1 year 34% lower incidence at 10 years Classical efficacy study (T1 T2) Oral GTT as the screening tool Very intensive, expensive one-on-one intervention Educated population, all literate Overweight/obesity assumed important mediator 18/24 18

20 Why Research Beyond the classical RCT? DPP efficacy study notwithstanding, diabesity epidemic marches on Lawrence Latino DPP (LLDPP) community-based effectiveness study real world 252 at risk pts randomized Group-based less intensive intervention Inexpensive 30 % of population illiterate in Spanish and English 19/24

21 DPP vs. LLDPP outcomes at 1 year Improvements in Outcomes at 1 year * DPP LDPPP Weight (lbs) HgbA1c (%) * Numbers approximate; personal communication from I Ockene Why similar effect of intervention on hyperglycemia, yet much weaker effect on weight???? 20

22 Why different effects LLDDP vs. DPP? Efficacy vs. effectiveness study? But effect on HgbA1c was similar Different populations? Some Latino groups, Native Americans know to be exquisitely sensitive to weight gain re diabetes incidence Are we seeing reverse effect here? Need to investigate mechanism that underlies these differences: genetics? 21/24

23 Bidirectionality Should our approach remain linear? T0 T1 T2 T3 T4 T5 OR Should transdisciplinary teams implement true bidirectionality? 22

24 Team Science, Bidirectionality T5 T0 Health Care T4 Molecules T1 Population Health T3 T2 23

25 3 Historical Examples of Bidirectionality Rutter and Plomin, Psychol Med 2009 Tobacco and lung cancer First: Epidemiologic studies Doll and Hill, BMJ 1950 and 1954 Later: clinical and animal studies, then gene expression studies Wen, Mod Path 2011 Lipids and heart disease Initial rabbit studies ignored (1913) Epidemiologic evidence in 1956 Basic lab research in 70s: model of how LDL causes atherosclerotic lesions LRC trial in the 80s, large statin RCTs in 90 s Fetal alcohol syndrome Clinical observations define syndrome Kl Jones, Lancet 1973 Mice studies confirm 24/24

26 SUMMARY Translational research is Transdisciplinary Bidirectional Driven by the need to move from knowledge for the sake of knowledge to realized human benefit Reminds us that Science without conscience is the soul s perdition Rabelais, Pantagruel, /24

27 QUESTIONS????? 26/24

28 Charge for the Day Look for bidirectionality Keynote lecture Mini-symposia Posters Think transdisciplinary teams Next presentation, lunch, coffee breaks Tell us how to do better Fill-out evaluations HAVE FUN All day long and evening reception with posters 5 prizes for best posters at evening reception